Uterine contractility is affected by a variety of hormones and other factors. The estrogen/progesterone ratio, the beta-adrenergic/beta-adrenergic receptor ratio and the prostaglandin content have all been implicated in influencing pregnant and nonpregnant uterine contractility. Substances such as beta-adrenergic agents relax the rat uterus; this action is accompanied by an elevation in cAMP levels, protein kinase activation and increase in bound cAMP in the tissue. Both cAMP and beta-adrenergic agents increase calcium uptake by microsomal vesicles prepared from uterus. Some actions of beta-adrenergic agents and some other relaxants may not involve the mediation of cAMP. Agents such as prostaglandins and oxytocin, which cause the uterus to contract, antagonize the relaxant-generated cAMP levels under specific conditions. The objective of the present study is to define the molecular mechanisms through which relaxin, a polypeptide with uterine relaxant activity originating in the corpus luteum, affects the uterus. We have previously shown that relaxin can inhibit spontaneous isometric contractions and elevate uterine cAMP, measured by radioimmunoassay. Catecholamine and local prostaglandin synthesis do not appear to mediate the cAMP elevating action. However, cAMP does not change under some conditions where relaxin causes muscle relaxation. To further explore the mechanisms by which relaxin affect the uterus, the effect of this hormone on bount cAMP, protein kinase activation ratio, Ca ion uptake, catecholamine content and microsomal protein phosphorylation will be studied. In vivo studies will be performed to substantiatethe in vitro findings and to investigate a possible role for relaxin in promoting the decreased responsiveness of the pregnant uterus.